Mixed alkylamido aluminate as a kinetically controlled base

Hiroshi Naka, James V. Morey, Joanna Haywood, Dana J. Eisler, Mary McPartlin, Felipe García, Hironaga Kudo, Yoshinori Kondo, Masanobu Uchiyama, Andrew E.H. Wheatley

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

The mechanisms by which directed ortho metalation (DoM) and postmetalation processes occur when aromatic compounds are treated with mixed alkylamido aluminate i-Bu3Al(TMP)Li (TMP-aluminate 1; TMP = 2,2,6,6- tetramethylpiperidide) have been investigated by computation and X-ray diffraction. Sequential reaction of ArC(=O)N(i-Pr)2 (Ar = phenyl, 1-naphthyl) with t-BuLi and i-Bu3Al in tetrahydrofuran affords [2-(i-Bu3Al)CmHnC(=O)N(i-Pr) 2]Li·3THF (m = 6, n = 4, 7; m = 10, n = 6, 8). These data advance the structural evidence for ortho-aluminated functionalized aromatics and represent model intermediates in DoM chemistry. Both 7 and 8 are found to resist reaction with HTMP, suggesting that ortho-aluminated aromatics are incapable of exhibiting stepwise deprotonative reactivity of the type recently shown to pertain to the related field of ortho zincation chemistry. Density functional theory calculations corroborate this view and reveal the existence of substantial kinetic barriers both to one-step alkyl exchange and to amido-alkyl exchange after an initial amido deprotonation reaction by aluminate bases. Rationalization of this dichotomy comes from an evaluation of the inherent Lewis acidities of the Al and Zn centers. As a representative synthetic application of this high kinetic reactivity of the TMP-aluminate, the highly regioselective deprotonative functionalization of unsymmetrical ketones both under mild conditions and at elevated temperatures is also presented.

Original languageEnglish
Pages (from-to)16193-16200
Number of pages8
JournalJournal of the American Chemical Society
Volume130
Issue number48
DOIs
Publication statusPublished - 2008 Dec 3

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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